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Bupivacaine (Liposomal)

Medically reviewed by Last updated on Oct 26, 2020.


(byoo PIV a kane lye po SO mal)

Index Terms

  • Bupivacaine Liposome
  • Bupivacaine Liposome/Pf
  • DepoFoam Bupivacaine
  • Exparel
  • Liposomal Bupivacaine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Injection:

Exparel: 1.3% (10 mL, 20 mL)

Brand Names: U.S.

  • Exparel

Pharmacologic Category

  • Local Anesthetic


Blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction.


Systemic absorption varies; dependent on dose, route of administration, and vascularity of administration site


Hepatic via conjugation; major metabolite pipecoloxylidine (PPX; inactive)


Urine (~6% unchanged)

Onset of Action

Rapid (Hu 2013)

Time to Peak

Within 1 hour (initial peak); 12 to 36 hours (second peak) (Hu 2013)

Duration of Action

Local: Up to 72 hours (Hu 2013); Systemic: Plasma levels can persist for 96 hours after local administration and 120 hours after interscalene brachial plexus nerve block.

Half-Life Elimination

13 to 34 hours (Hu 2013)

Protein Binding


Special Populations: Renal Function Impairment

Renal impairment may reduce bupivacaine elimination increasing systemic exposure.

Special Populations: Hepatic Function Impairment

Severe impairment may reduce bupivacaine metabolism increasing systemic exposure.

Use: Labeled Indications

Analgesia, postsurgical: Single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia.


Obstetrical paracervical block anesthesia

Dosing: Adult

Note: Bupivacaine (liposomal) is not bioequivalent to bupivacaine hydrochloride; dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) or vice versa is not possible.

Analgesia, postsurgical:

Local anesthesia: Infiltration: Single dose: Dose is based on size of surgical site, volume required to cover the area, and individual patient factors (maximum dose: 266 mg [20 mL]). General dosage guidance for bunionectomy and hemorrhoidectomy provided below:

Bunionectomy: 7 mL of undiluted bupivacaine (liposomal) infiltrated into the tissues surrounding the osteotomy and 1 mL of undiluted bupivacaine (liposomal) infiltrated into the subcutaneous tissue of the surgical site (total dose = 106 mg [8 mL])

Hemorrhoidectomy: 30 mL of diluted bupivacaine (liposomal) (20 mL diluted with 10 mL NS) divided and infiltrated as 6 injections of 5 mL each (total dose = 266 mg [20 mL]) around the anal sphincter.

Regional analgesia: Interscalene brachial plexus nerve block: Single dose:

Total shoulder arthroplasty or rotator cuff repair: 133 mg (10 mL)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.


Invert vial several times prior to withdrawing contents to resuspend particles. May dilute with NS or LR up to a final concentration of 0.89 mg/mL (ie, a 1:14 dilution by volume). Use only NS or LR for dilution; use of water or other hypotonic agents will disrupt liposomal particles. Do not admix with other local anesthetics (except for bupivacaine hydrochloride) or drugs. Bupivacaine hydrochloride may be mixed in the same syringe as bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.


Administer undiluted or diluted. Inject slowly (1 to 2 mL per injection) into the surgical site using a ≥25 gauge needle with frequent aspiration prior to and during administration; do not filter. Do not administer epidurally, intrathecally, intravascularly, intra-articularly, or as a regional nerve block (except interscalene brachial plexus nerve block). Do not allow bupivacaine (liposomal) to come into contact with antiseptics (eg, povidone iodine) in solution; when a topical antiseptic is applied, allow site to dry prior to injection.

Non-bupivacaine-based local anesthetics may cause an immediate release of bupivacaine (liposomal) if administered together locally; therefore, bupivacaine should be administered no sooner than 20 minutes after injection of lidocaine. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration; bupivacaine hydrochloride may be administered simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.


Store intact vials at 2°C to 8°C (36°F to 46°F); may also store at 20°C to 25°C (68°F to 77°F) for up to 30 days (do not re-refrigerate); do not heat or autoclave vials before use. Following withdrawal from the vial, store at 20°C to 25°C (68°F to 77°F) up to 4 hours prior to administration. Diluted suspensions must be used within 4 hours of preparation. Do not freeze or expose to high temperature (>40°C [104°F]) for an extended period of time or administer if suspected of being frozen or exposed to high temperatures. Discard any unused portion.

Drug Interactions

Bupivacaine: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Bupivacaine may be administered immediately before, or administered in the same admixture syringe as liposomal bupivacaine as long as the ratio of the milligram dose of bupivacaine to liposomal bupivacaine does not exceed 1:2. Consider therapy modification

Hyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Monitor therapy

Lidocaine (Systemic): May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with topical lidocaine. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine. Consider therapy modification

Local Anesthetics: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics, but may be administered 20 minutes or more after lidocaine. Avoid all local anesthetics within 96 hours after administration of liposomal bupivacaine. Avoid combination

Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy

Neuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Technetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.


Central nervous system: Motor dysfunction (12% to 21%)

Gastrointestinal: Nausea (<40%), vomiting (28%), constipation (2% to 22%)

Miscellaneous: Fever (2% to 23%)

1% to 10%:

Cardiovascular: Hypertension (<10%; includes procedural hypertension), hypotension (7%), procedural hypotension (4%), tachycardia (4%), peripheral edema (2% to 3%), sinus tachycardia (2% to 3%), atrial fibrillation (<2%), bradycardia (<2%), bundle branch block (<2%), cardiac arrhythmia (<2%), deep vein thrombosis (<2%), edema (<2%), first degree atrioventricular block (<2%), oxygen saturation decreased (<2%), orthostatic hypotension (<2%), palpitations (<2%), presyncope (<2%), prolonged QT interval on ECG (<2%), sinus bradycardia (<2%), supraventricular extrasystole (<2%), syncope (2%), ventricular premature contractions (<2%), ventricular tachycardia (<2%)

Central nervous system: Insomnia (2% to <10%), procedural pain (2% to <10%), headache (4% to 8%), dizziness (≤6%; includes postural dizziness), confusion (5%), fatigue (5%), drowsiness (2% to 5%), hypoesthesia (2% to 4%), anxiety (3%), sensation of cold (3%), falling (2% to 3%), feeling hot (2%), mobility disorder (decreased: 2%), sensation disorder (sensory loss: 2%), agitation (<2%), chills (<2%), delirium (<2%), depression (<2%), hyperthermia (<2%), myasthenia (<2%), pain (<2%), paresthesia (<2%), restlessness (<2%), sedation (<2%), lethargy (1%)

Dermatologic: Hyperhidrosis (5%), pruritus (3%), cellulitis (<2%), diaphoresis (<2%), erythema (<2%), increased wound secretion (<2%), pallor (<2%), pruritic rash (<2%), skin blister (<2%), skin rash (<2%), urticaria (<2%)

Gastrointestinal: Dysgeusia (7%), oral hypoesthesia (3% to 4%), hiccups (1% to 2%)

Genitourinary: Urinary retention (8%), dysuria (<2%), urinary incontinence (<2%)

Hematologic & oncologic: Acute posthemorrhagic anemia (2% to <10%; postoperative), anemia (6%), bruise (≤2%), hematoma (<2%), leukocytosis (<2%), postoperative hematoma (≤2%)

Hepatic: Increased liver enzymes (4%), increased serum aspartate aminotransferase (3%), increased serum alanine aminotransferase (1%)

Hypersensitivity: Fixed drug eruption (<2%), hypersensitivity reaction (<2%)

Infection: Fungal infection (2%)

Local: Localized edema (incision site: <2%)

Neuromuscular & skeletal: Back pain (<10%), muscle spasm (<10%), muscle twitching (8%), arthralgia (<2%), asthenia (<2%), joint swelling (<2%), laryngospasm (<2%), musculoskeletal pain (<2%), neck pain (<2%), tremor (<2%)

Ophthalmic: Blurred vision (<2%), decreased visual acuity (<2%)

Otic: Auditory impairment (<2%), tinnitus (<2%)

Renal: Increased serum creatinine (2%)

Respiratory: Hypoxia (1% to 2%), apnea (<2%), atelectasis (<2%), cough (<2%), dyspnea (<2%), pulmonary infiltrates (<2%), pneumonia (<2%), pulmonary infection (<2%), respiratory depression (<2%), respiratory failure (<2%)

Miscellaneous: Procedural complications (postprocedural swelling: 2%), dehiscence (<2%)

<1%, postmarketing, and/or case reports: Paralysis, seizure


Concerns related to adverse effects:

• CNS effects: CNS effects (including excitation and/or depression) may occur, possibly leading to convulsions, unconsciousness, and/or respiratory arrest; may be related to total dose administered, route of administration, and physical status of patient; monitor for CNS-related changes or alterations in consciousness after each injection. Additionally, use of local anesthetics have been associated with neurologic effects following infiltration of soft tissue (persistent anesthesia, paresthesia weakness, paralysis), which may be irreversible.

• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, twitching, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Sensory and/or motor loss is temporary and varies and may last up to 5 days.

• Cardiovascular toxicity: Serious and fatal cardiovascular system reactions (eg, decreased cardiac output and arterial blood pressure, atrioventricular block, ventricular arrhythmias, cardiac arrest) may occur with toxic concentrations.

• Hypersensitivity reactions: Allergic-type reactions (eg, angioneurotic edema [including laryngeal edema], dizziness, elevated temperature, excessive sweating, nausea, syncope, tachycardia, pruritus, erythema, sneezing, urticaria, vomiting) and possibly anaphylactoid-like symptoms (including severe hypotension) have been reported (rare); cross-sensitivity among amide-type local anesthetics has been reported.

• Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily in the shoulder joint) has occurred following infusion, with some cases requiring arthroplasty or shoulder replacement.

• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).

• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.

• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have been reported with local anesthetics.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; patients with impaired cardiovascular function are less able to compensate for functional changes associated with AV conduction prolongation produced by bupivacaine.

• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with severe impairment may be at greater risk for toxicity.

• Renal impairment: Use with caution in patients with renal impairment; may be at greater risk for toxicity.

Other warnings/precautions:

• Appropriate use: Avoid intravascular, epidural, intrathecal, intra-articular, and regional nerve block (except interscalene brachial plexus nerve block) injections. Not indicated for preincisional or preprocedural locoregional anesthetic techniques that require deep and complete sensory block. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration. Aspiration should must be performed frequently prior to and during administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

• Product interchangeability: Bupivacaine hydrochloride is not bioequivalent to bupivacaine (liposomal); dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) and vice versa is not possible.

• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.

Monitoring Parameters

Cardiovascular and respiratory (adequacy of ventilation) vital signs, state of consciousness; signs of CNS toxicity, pain relief.

Pregnancy Considerations

Bupivacaine crosses the placenta.

Following use of the nonliposomal formulation, small amounts of bupivacaine can be found in the maternal plasma, potentially causing varying degrees of maternal, fetal, and neonatal toxicity involving the CNS, peripheral vascular tone, and cardiac function.

Liposomal bupivacaine is approved for postsurgical local analgesia; studies have evaluated its use for intra-incisional blocks at the time of cesarean delivery to decrease postoperative pain (Parikh 2019; Prabhu 2018). Use of bupivacaine in obstetrical paracervical block anesthesia is contraindicated (may cause fetal bradycardia and death).

Patient Education

What is this drug used for?

• It is used to ease pain at the surgery site.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Trouble sleeping

• Muscle spasms

• Hiccups

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe headache

• Dizziness

• Passing out

• Vision changes

• Methemoglobinemia like blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath.

• Change in balance

• Agitation

• Anxiety

• Change in speech

• Change in taste

• Lightheadedness

• Fatigue

• Confusion

• Blurred vision

• Noise or ringing in the ears

• Tremors

• Twitching

• Depression

• Seizures

• Nausea

• Vomiting

• Chills

• Small pupils

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Sneezing

• Sweating a lot

• Joint pain

• Joint rigidity

• Weakness

• Numbness

• Tingling

• Swelling of arms or legs

• Trouble urinating

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.